Progabide (

INN Inns are generally establishments or buildings where travelers can seek lodging, and usually, food and drink. Inns are typically located in the country or along a highway; before the advent of motorized transportation they also provided accommo ...

; trade name Gabrene,

Sanofi-Aventis Sanofi S.A. is a French multinational pharmaceutical and healthcare company headquartered in Paris, France. Originally, the corporation was established in 1973 and merged with Synthélabo in 1999 to form Sanofi-Synthélabo. In 2004, Sanofi-Syn ...

) is an analogue and prodrug of γ-aminobutyric acid (GABA) used in the treatment of

epilepsy Epilepsy is a group of non-communicable neurological disorders characterized by recurrent epileptic seizures. Epileptic seizures can vary from brief and nearly undetectable periods to long periods of vigorous shaking due to abnormal electrica ...

. Via conversion into GABA, progabide behaves as an agonist of the GABA_A, GABA_B, and GABA_A-ρ receptors.

Uses

Progabide is approved in

France France (), officially the French Republic ( ), is a country primarily located in Western Europe. It also comprises of overseas regions and territories in the Americas and the Atlantic, Pacific and Indian Oceans. Its metropolitan area ...

for either monotherapy or adjunctive use in the treatment of epilepsy—specifically, generalized tonic-clonic, myoclonic, partial, and Lennox-Gastaut syndrome seizures—in both children and adults. Progabide has been investigated for many diseases besides epilepsy, including

Parkinson's disease Parkinson's disease (PD), or simply Parkinson's, is a long-term degenerative disorder of the central nervous system that mainly affects the motor system. The symptoms usually emerge slowly, and as the disease worsens, non-motor symptoms becom ...

schizophrenia Schizophrenia is a mental disorder characterized by continuous or relapsing episodes of psychosis. Major symptoms include hallucinations (typically hearing voices), delusions, and disorganized thinking. Other symptoms include social wit ...

clinical depression Major depressive disorder (MDD), also known as clinical depression, is a mental disorder characterized by at least two weeks of pervasive low mood, low self-esteem, and loss of interest or pleasure in normally enjoyable activities. Intro ...

, anxiety disorder and

spasticity Spasticity () is a feature of altered skeletal muscle performance with a combination of paralysis, increased tendon reflex activity, and hypertonia. It is also colloquially referred to as an unusual "tightness", stiffness, or "pull" of muscles ...

with various levels of success. In 1987, Bartolini and colleagues reported progabide's actions on dopamine to be contradictory, decreasing dopamine release, dopamine receptor density and postsynaptic receptor responsivity to dopamine while reducing striatal cholinergic activity so as to increase dopaminergic effects. Bartholini and colleagues concluded that it was this that caused Parkinson's patients in human clinical trials to either see an improvement in their Parkinson's with a worsening of L-dopa dyskinesia or an improvement in dyskinesia but with sometimes aggravated Parkinson's symptoms. The cholinergic effect takes only a single injection to achieve in rats; when given with

haloperidol Haloperidol, sold under the brand name Haldol among others, is a typical antipsychotic medication. Haloperidol is used in the treatment of schizophrenia, tics in Tourette syndrome, mania in bipolar disorder, delirium, agitation, acute psychosi ...

, the development of tolerance to haloperidol's

cataleptic Catalepsy (from Ancient Greek , , "seizing, grasping") is a nervous condition characterized by muscular rigidity and fixity of posture regardless of external stimuli, as well as decreased sensitivity to pain. Signs and symptoms Symptoms inc ...

effects did not develop. It was hoped that this would be effective for

tardive dyskinesia Tardive dyskinesia (TD) is a disorder that results in involuntary repetitive body movements, which may include grimacing, sticking out the tongue or smacking the lips. Additionally, there may be rapid jerking movements or slow writhing movemen ...

. However, Soares, Rathbone and Deeks wrote in the 2004 issue of ''The Cochrane Database of Systematic Reviews'' that "Any possible benefits are likely to be outweighed by the adverse effects associated with their ABAergic agents'use." In addition to being tested for antipsychotic-induced tardive dyskinesia, progabide was itself tested as an antipsychotic; as early as 1979, it was obvious that it was ineffective for

psychosis Psychosis is a condition of the mind that results in difficulties determining what is real and what is not real. Symptoms may include delusions and hallucinations, among other features. Additional symptoms are incoherent speech and behavior ...

. (French) While progabide may have been devoid of antipsychotic effects, it did have the effect in schizoaffective and hebephrenic patients of improving environmental responsiveness and social interactions.

Synthesis

References

{{GABAergics Anticonvulsants Chlorobenzenes GABA analogues GABAA receptor agonists GABAA-rho receptor agonists GABAB receptor agonists Fluoroarenes Phenols Imines

Uses

Synthesis

See also

References